Chemotaxis of alveolar macrophages in response to signals derived from alveolar epithelial cells

Abstract

We have postulated that alveolar epithelial cells (AEC) play a critical role in local regulation of alveolar macrophage (AM) recruitment and activation for host defense in the lung. The present study explores the effects of conditioned medium from AEC (AEC-CM) on the migration of AM, using a Boyden chamber assay. AECCM was chemotactic for AM, with peak activity observed with a 1:10 dilution. We previously showed that rat AEC express the chemokines RANTES (regulated on activation, normal T expressed and secreted) and monocyte chemoattractant protein 1 (MCP-1) as well as granulocyte-macrophage colony-stimulating factor (GMCSF). Neutralizing antibodies to RANTES and to MCP-1 and immunoprecipitation of GM-CSF decreased the chemotactic activity of AEC-CM by 58%, 29%, and 47%, respectively. Similar levels of chemotaxis were found in response to recombinant RANTES, MCP-1, and GM-CSF. In each instance the optimal dose was very low (0.01 to 0.1 ng/ml), with diminished chemotaxis at higher doses. Peritoneal macrophages (PM) also migrated in response to AEC-CM and each of the recombinant cytokines; however, AM were much more sensitive to AEC-CM, RANTES, and GM-CSF than were PM. AM migrated preferentially from medium conditioned by unstimulated AEC toward supernatants from interleukin 1α-stimulated AEC. Therefore, AEC may control the distribution of AM through the creation of local chemotactic gradients and are likely to play a critical role in the host response to low-level antigen entry into the peripheral lung.